Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.HIV Antibodies: Antibodies reactive with HIV ANTIGENS.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).HIV Envelope Protein gp120: External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Antigens, CD4: 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.Neutralization Tests: The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Small Molecule Libraries: Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Binding Sites, Antibody: Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Immunoglobulin Fab Fragments: Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.Immunoglobulin Fragments: Partial immunoglobulin molecules resulting from selective cleavage by proteolytic enzymes or generated through PROTEIN ENGINEERING techniques.Drug Discovery: The process of finding chemicals for potential therapeutic use.Antibodies, Anti-Idiotypic: Antibodies which react with the individual structural determinants (idiotopes) on the variable region of other antibodies.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Epitopes: Sites on an antigen that interact with specific antibodies.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Antibodies, Bispecific: Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Immunoglobulin Fc Fragments: Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Antigens: Substances that are recognized by the immune system and induce an immune reaction.Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.Immunoglobulin Heavy Chains: The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa.Immunoglobulin Light Chains: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.Dinitrophenols: Organic compounds that contain two nitro groups attached to a phenol.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Immunoglobulin Constant Regions: The domains of the immunoglobulin molecules that are invariable in their amino acid sequence within any class or subclass of immunoglobulin. They confer biological as well as structural functions to immunoglobulins. One each on both the light chains and the heavy chains comprises the C-terminus half of the IMMUNOGLOBULIN FAB FRAGMENT and two or three of them make up the rest of the heavy chains (all of the IMMUNOGLOBULIN FC FRAGMENT)Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Immunoglobulins: Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.Kinetics: The rate dynamics in chemical or physical systems.Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell.Antibodies, Neoplasm: Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.Iodine Isotopes: Stable iodine atoms that have the same atomic number as the element iodine, but differ in atomic weight. I-127 is the only naturally occurring stable iodine isotope.Antibodies, Protozoan: Immunoglobulins produced in a response to PROTOZOAN ANTIGENS.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.gamma-Globulins: Serum globulins that migrate to the gamma region (most positively charged) upon ELECTROPHORESIS. At one time, gamma-globulins came to be used as a synonym for immunoglobulins since most immunoglobulins are gamma globulins and conversely most gamma globulins are immunoglobulins. But since some immunoglobulins exhibit an alpha or beta electrophoretic mobility, that usage is in decline.Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Immunoglobulin M: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Mice, Inbred BALB CAntibodies, Fungal: Immunoglobulins produced in a response to FUNGAL ANTIGENS.Immunoglobulin kappa-Chains: One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.Single-Chain Antibodies: A form of antibodies consisting only of the variable regions of the heavy and light chains (FV FRAGMENTS), connected by a small linker peptide. They are less immunogenic than complete immunoglobulin and thus have potential therapeutic use.Antibodies, Blocking: Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)Molecular Weight: The sum of the weight of all the atoms in a molecule.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.Antibodies, Catalytic: Antibodies that can catalyze a wide variety of chemical reactions. They are characterized by high substrate specificity and share many mechanistic features with enzymes.Antibodies, Heterophile: Antibodies elicited in a different species from which the antigen originated. These antibodies are directed against a wide variety of interspecies-specific antigens, the best known of which are Forssman, Hanganutziu-Deicher (H-D), and Paul-Bunnell (P-B). Incidence of antibodies to these antigens--i.e., the phenomenon of heterophile antibody response--is useful in the serodiagnosis, pathogenesis, and prognosis of infection and latent infectious states as well as in cancer classification.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Fluorescent Antibody Technique, Indirect: A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. (From Bennington, Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Immunoglobulin A: Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Antibodies, Monoclonal, Humanized: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Antibodies, Antiphospholipid: Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC;), ANTIPHOSPHOLIPID SYNDROME; related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Bacterial Proteins: Proteins found in any species of bacterium.Time Factors: Elements of limited time intervals, contributing to particular results or situations.HIV Envelope Protein gp41: Transmembrane envelope protein of the HUMAN IMMUNODEFICIENCY VIRUS which is encoded by the HIV env gene. It has a molecular weight of 41,000 and is glycosylated. The N-terminal part of gp41 is thought to be involved in CELL FUSION with the CD4 ANTIGENS of T4 LYMPHOCYTES, leading to syncytial formation. Gp41 is one of the most common HIV antigens detected by IMMUNOBLOTTING.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Mice, Inbred C57BLAntigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Immunoassay: A technique using antibodies for identifying or quantifying a substance. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance.Immunization, Passive: Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Cell Adhesion: Adherence of cells to surfaces or to other cells.Cytokine Receptor gp130: A cytokine receptor that acts through the formation of oligomeric complexes of itself with a variety of CYTOKINE RECEPTORS.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Immunologic Techniques: Techniques used to demonstrate or measure an immune response, and to identify or measure antigens using antibodies.Immunosorbent Techniques: Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Immunoglobulin Idiotypes: Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains.Hemagglutination Tests: Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed)Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Complement Fixation Tests: Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Hemagglutination Inhibition Tests: Serologic tests in which a known quantity of antigen is added to the serum prior to the addition of a red cell suspension. Reaction result is expressed as the smallest amount of antigen which causes complete inhibition of hemagglutination.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Cell Line, Tumor: A cell line derived from cultured tumor cells.Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.Viral Envelope Proteins: Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Antibodies, Antineutrophil Cytoplasmic: Autoantibodies directed against cytoplasmic constituents of POLYMORPHONUCLEAR LEUKOCYTES and/or MONOCYTES. They are used as specific markers for GRANULOMATOSIS WITH POLYANGIITIS and other diseases, though their pathophysiological role is not clear. ANCA are routinely detected by indirect immunofluorescence with three different patterns: c-ANCA (cytoplasmic), p-ANCA (perinuclear), and atypical ANCA.Viral Proteins: Proteins found in any species of virus.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Seroepidemiologic Studies: EPIDEMIOLOGIC STUDIES based on the detection through serological testing of characteristic change in the serum level of specific ANTIBODIES. Latent subclinical infections and carrier states can thus be detected in addition to clinically overt cases.Spleen: An encapsulated lymphatic organ through which venous blood filters.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Isoantibodies: Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.Antibody Diversity: The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Immunoglobulin Isotypes: The classes of immunoglobulins found in any species of animal. In man there are nine classes that migrate in five different groups in electrophoresis; they each consist of two light and two heavy protein chains, and each group has distinguishing structural and functional properties.Complement System Proteins: Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Hepatitis C Antibodies: Antibodies to the HEPATITIS C ANTIGENS including antibodies to envelope, core, and non-structural proteins.Antibodies, Monoclonal, Murine-Derived: Antibodies obtained from a single clone of cells grown in mice or rats.Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.HIV Envelope Protein gp160: An envelope protein of the human immunodeficiency virus that is encoded by the HIV env gene. It has a molecular weight of 160,000 kDa and contains numerous glycosylation sites. It serves as a precursor for both the HIV ENVELOPE PROTEIN GP120 and the HIV ENVELOPE PROTEIN GP41.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Hepatitis B Antibodies: Antibodies to the HEPATITIS B ANTIGENS, including antibodies to the surface (Australia) and core of the Dane particle and those to the "e" antigens.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Oligopeptides: Peptides composed of between two and twelve amino acids.Immunity, Maternally-Acquired: Resistance to a disease-causing agent induced by the introduction of maternal immunity into the fetus by transplacental transfer or into the neonate through colostrum and milk.Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies.Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Insulin Antibodies: Antibodies specific to INSULIN.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.Antibody-Dependent Cell Cytotoxicity: The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Microscopy, Immunoelectron: Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.

*Env (gene)

"Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary ... It is originally buried within the viral envelope, but when gp120 binds to a CD4 receptor, gp120 changes its conformation ... Prior to binding the host cell, gp120 remains effectively hidden from antibodies because it is buried in the protein and ... Since CD4 receptor binding is the most obvious step in HIV infection, gp120 was among the first targets of HIV vaccine research ...

*Abzyme

If an antibody is developed to bind to a molecule that's structurally and electronically similar to the transition state of a ... at Houston announced that they have engineered an abzyme that degrades the superantigenic region of the gp120 CD4 binding site ... The abzyme does more than bind to the site, it catalytically destroys the site, rendering the virus inert, and then can attack ... By raising an antibody to bind to a stable transition-state analog, a new and unique type of enzyme is produced. So far, all ...

*Envelope glycoprotein GP120

Many neutralizing antibodies bind to sites located in variable regions of gp120, so mutations in these regions will be selected ... Consequently, anything which binds to gp120 or its targets can physically block gp120 from binding to a cell. Only one such ... Fostemsavir (BMS-663068) is a methyl phosphate prodrug of the small molecule inhibitor BMS-626529, which prevents viral entry ... The presence of large carbohydrate chains extending from gp120 might obscure possible antibody binding sites. The boundaries of ...

*PRO 140

The gp120 will bind CD4 and the CCR5co receptor molecule, and this triggers gp41-mediated fusion of the viral and cellular ... It prevents the virus-cell binding at a distinct site in the CCR5 co-receptor without interfering with its natural activity. ... PRO 140 is a lab-made antibody that functions as an entry inhibitor. PRO 140 binds to the CCR5 receptor on the CD4 cells, and ... PRO 140, a humanized form of a PA14 antibody, is a chemokine-receptor CCR5 monoclonal antibody and can inhibit CCR5 tropic HIV- ...

*Protein design

... residues outside of the binding interface between the gp120 HIV envelope protein and the formerly discovered b12-antibody were ... branch and bound algorithms bound the conformation space and explore only the promising branches. A popular search algorithm ... Individual water molecules can sometimes have a crucial structural role in the core of proteins, and in protein-protein or ... Further, positive and negative design was also used by Anderson and coworkers to predict mutations in the active site of a drug ...

*Gp41

These conformational changes start with gp120 that rearranges to expose the binding sites for the coreceptors mentioned above. ... Small-molecule inhibitors that are able to bind to two hydrophobic pockets at once have also been show to be 40-60 times more ... The structure is cage-like with a hollow center that inhibits antibody access. While gp120 sits on the surface of the viral ... Gp120 binds to a CD4 and a co-receptor (CCR5 or CXCR4), found on susceptible cells such as Helper T cells and macrophages. As a ...

*Cell adhesion

HIV has an adhesion molecule termed gp120 that binds to its ligand CD4, which is expressed on lymphocytes. The differential ... Viruses also have adhesion molecules required for viral binding to host cells. For example, influenza virus has a hemagglutinin ... Pemphigus is the result of auto-antibodies which target desmosomal cadherins, resulting in loss of cell adhesion. Cell adhesion ... Cells can form integrin-mediated attachment sites called focal adhesions, which provide the necessary mechanical force for ...

*Antibody-dependent enhancement

The viruses bind to the antigen binding site at the other end of the antibody. ADE is common in cells cultured in the ... The deposition of complement on the virus brings the gp120 protein close to CD4 molecules on the surface of the cells, thus ... but the antibody bound to virus also binds to the receptor of the cell, the Fc-region antibody receptor FcγR. This brings the ... The antiviral proteins (i.e., the antibodies) bind to antibody Fc receptors that some of these cells have in the plasma ...

*Entry inhibitor

TNX-355, a monoclonal antibody that binds CD4 and inhibits the binding of gp120 PRO 140, a monoclonal antibody that binds CCR5 ... "Neutralizing antibody and anti-retroviral drug sensitivities of HIV-1 isolates resistant to small molecule CCR5 inhibitors". ... among others sites, the GP41 transmembrane glycoprotein. The trials are being conducted by Virionyx, a New Zealand Company. VIR ... It has been found to bind to gp120 at the exact region, or epitope, where gp120 binds to CD4. b12 seems to serve as a natural ...

*Sulfatide

The binding of gp120 to GalCer has the ability to start the fusion of HIV-1, but the binding of gp120 to sulfatide does not. ... First, sulfatide binds to tenascin-R or laminin in the extracellular matrix, which goes on to bind signaling molecules such as ... This is caused by the binding of the anti-sulfatide antibodies to the surface of the myelin sheath and/or the surface of ... suggesting that the T cells are presented with myelin lipids by CD1 molecules at sites of inflammation. Sulfatide has roles in ...

*HLA-DMA

... role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. ... 1994). "HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same face of CD4". J. Immunol. 152 (9): 4475- ... 1994). "HIV-1 gp41 binding proteins and antibodies to gp41 could inhibit enhancement of human Raji cell MHC class I and II ... 1995). "HIV gp120 inhibits T cell activation by interfering with expression of costimulatory molecules CD40 ligand and CD80 ( ...

*FCAR

... is sterically hindered in its binding to FcαRI. This is because some of sIgA's FcαRI binding site is obscured by a section of ... A pro-inflammatory response is signaled when IgA molecules in an immune complex bind to multiple FcαRI, resulting in the ... FcαRI binds the heavy-chain constant region of Immunoglubulin A (IgA) antibodies. FcαRI is present on the cell surface of ... Dürrbaum-Landmann I, Kaltenhäuser E, Flad HD, Ernst M (April 1994). "HIV-1 envelope protein gp120 affects phenotype and ...

*DNA vaccination

Secreted or plasma membrane-bound antigens are more effective at inducing antibody responses than cytosolic antigens, while ... CTL responses can be enhanced by co-inoculation with co-stimulatory molecules such as B7-1 or B7-2 for DNA vaccines against ... Bennett, R.M.; Gabor, G.T.; Merritt, M.M. (1985). "DNA binding to human leukocytes. Evidence for a receptor-mediated ... Torres CA, Iwasaki A, Barber BH, Robinson HL (May 1997). "Differential dependence on target site tissue for gene gun and ...

*HLA-DMB

... molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, ... 1994). "HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same face of CD4". J. Immunol. 152 (9): 4475- ... 1994). "HIV-1 gp41 binding proteins and antibodies to gp41 could inhibit enhancement of human Raji cell MHC class I and II ... 1995). "HIV gp120 inhibits T cell activation by interfering with expression of costimulatory molecules CD40 ligand and CD80 ( ...

*Tyrosine phosphorylation

Similarities between the inhibitory effects of anti-CD4 antibodies and HIV-derived gp 120 immune complexes on T-cells suggest ... Insulin binds to the insulin receptor at the cell surface and activates its tyrosine kinase activity, leading to ... Binding of PLCγ to the activated receptor facilitates its efficient tyrosine phosphorylation by the RTK. PDGF-induced ... Phosphorylation of selected tyrosine sites on receptor substrates is known to activate different pathways leading to increased ...

*Neutralizing antibody

Gp120 and gp41 assemble as a trimer. The bNAbs binding site occurs only on the trimer structure, the form of Evn that invades ... while binding antibodies flag antigens. This difference can be shown with IFN-beta (IFN-β); "Antibodies can simply bind to IFN- ... Most mutations that shape bNAbs take place at the tips of the Y-shaped antibody molecules, which have loops to ensnare viral ... The difference between neutralizing antibodies and binding antibodies is that neutralizing antibodies neutralize the biological ...

*HLA-F

Upon immune cell activation, HLA-F binds free forms of HLA class I molecules and reaches the cell surface as heterodimer. In ... Chen YH, Böck G, Vornhagen R, Steindl F, Katinger H, Dierich MP (Sep 1994). "HIV-1 gp41 binding proteins and antibodies to gp41 ... Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, the putative peptide binding sites, ... "Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV-1 gp120". European Journal of Immunology ...

*Macrophage

HIV can enter the macrophage through binding of gp120 to CD4 and second membrane receptor, CCR5 (a chemokine receptor). Both ... a B-cell in the lymph node recognizes the same unprocessed surface antigen on the bacterium with its surface bound antibody, ... molecule nitric oxide, whereas rodent M2 macrophages have the unique ability to metabolize arginine to the "repair" molecule ... pathogens and cytokines released by macrophages already at the site. At some sites such as the testis, macrophages have been ...

*Feline coronavirus

... neutralizing oligo-saccharides binding sialic acid decreases when it binds increasingly to glycoproteins. (The APN is a ... Dr ADDIE website focused research about FIP Coronavirus Site général Coronavirus site général Coronavirus Pictures. ... However, several questions arise: If this protection is only supported by maternal antibodies, why are these antibodies not ... Coronaviruses bind to macrophages via the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC- ...

*Secreted frizzled-related protein 1

The GLI-binding site was identified within the 5'-flanking promoter region of the human SFRP1 gene. The GLI-binding site was ... They bind by ionic interactions with a variety of proteins. Heparin is widely used as an injectable anticoagulant. SFRP1 are ... Similar to anti-Wnt antibodies, treatment with recombinant SFRP1 inhibited growth of SNU 1076 cells as well. This suggests that ... FRP-1 and 4F2/CD98 are identical molecules". J. Immunol. 155 (7): 3585-92. PMID 7561057. Ohgimoto S, Tabata N, Suga S, ...

*Structure and genome of HIV

The V3 loop of the viron's envelope glycoprotein, gp120, allows it to infect human immune cells by binding to a cytokine ... The interactions of the gp120 V3 loop of different HIV-1 strains with the potent anti-HIV human monoclonal antibody 447-52D. ... The Rev protein binds to the viral genome via an arginine-rich RNA-binding motif that also acts as a NLS (nuclear localization ... Rong, L; Russell RS; Hu J; Laughrea M; Wainberg MA; Liang C (2003). "Deletion of stem-loop 3 is compensated by second-site ...

*Seth Lederman

"Dextran sulfate and heparin interact with CD4 molecules to inhibit the binding of coat protein (gp120) of HIV". J. Immunol. 143 ... "Protein recognized by an antibody that specifically binds an epitope that is specifically bound by monoclonal antibody 5c8". ... "Department of Medicine Faculty". Columbia University website. Retrieved 30 January 2012. "Research Faculty - Seth Lederman, M.D ... "Protein recognized by an antibody that specifically binds an epitope that is specifically bound by monoclonal antibody 5c8", ...
The membrane proximal external region (MPER) of the gp41 subunit of the HIV-1 envelope glycoprotein (Env) contains determinants for broadly neutralizing antibodies and has remained an important focus of vaccine design. However, creating an immunogen that elicits broadly neutralizing antibodies to this region has proven difficult in part due to the relative inaccessibility of the MPER in the native conformation of Env. Here, we describe the antigenicity and immunogenicity of a panel of oligomeric gp41 immunogens designed to model a fusion-intermediate conformation of Env in order to enhance MPER exposure in a relevant conformation. The immunogens contain segments of the gp41 N- and C-heptad repeats to mimic a trapped intermediate, followed by the MPER, with variations that include different N-heptad lengths, insertion of extra epitopes, and varying C-termini. These well-characterized immunogens were evaluated in two different immunization protocols involving ...
The Ethical and Scientific Considerations of Human Immunodeficiency Virus Antibody Screening in Volunteers for Clinical Pharmacologic ...
In this study, we established that after 3 years of infection, the frequency of individuals with neutralization breadth in the CAPRISA cohort was 17.5% (7/40 participants). In some individuals, cross-neutralizing antibodies appeared to target subtype-specific determinants, while in others these antibodies were aimed at more universal epitopes. Heterologous neutralizing antibodies first appeared in some individuals as early as 1 year postinfection but peaked at 4 years, with no increases thereafter. The number of viruses neutralized was associated with the viral load and CD4+ T cell count at set point (6 months postinfection) as well as with the drop in CD4+ T cell count between preinfection and 6 months, suggesting that early events in HIV infection set the stage for the development of breadth.. Broadly cross-neutralizing antibodies were produced in a small proportion of individuals within the CAPRISA cohort after 3 years of follow-up. The frequency and extent of neutralization breadth found in ...
The early autologous neutralizing antibody response in human immunodeficiency virus type 1 (HIV-1) subtype C infections is often characterized by high titers, but the response is type specific with little to no cross-neutralizing activity. The specificities of these early neutralizing antibodies are not known; however, the type specificity suggests that they may target the variable regions of the envelope. Here, we show that cross-reactive anti-V3 antibodies developed within 3 to 12 weeks in six individuals but did not mediate autologous neutralization. Using a series of chimeric viruses, we found that antibodies directed at the V1V2, V4, and V5 regions contributed to autologous neutralization in some individuals, with V1V2 playing a more substantial role. However, these antibodies did not account for the total neutralizing capacity of these sera against the early autologous virus. Antibodies directed against the C3-V4 region were involved in autologous neutralization in all ...
Failure to elicit broadly neutralizing (bNt) antibodies (Abs) against the membrane-proximal external region of HIV-1 gp41 (MPER) reflects the difficulty of mimicking its neutralization-competent structure (NCS). Here, we analyzed MPER antigenicity in the context of the plasma membrane and identified a role for the gp41 transmembrane domain (TM) in exposing the epitopes of three bNt monoclonal Abs (MAbs) (2F5, 4E10, and Z13e1). We transiently expressed DNA constructs encoding gp41 ectodomain fragments fused to either the TM of the platelet-derived growth factor receptor (PDGFR) or the gp41 TM and cytoplasmic tail domain (CT). Constructs encoding the MPER tethered to the gp41 TM followed by a 27-residue CT fragment (MPER-TM1) produced optimal MAb binding. Critical binding residues for the three Nt MAbs were identified using a panel of 24 MPER-TM1 mutants bearing single amino acid substitutions ...
An understanding of how broadly neutralizing activity develops in HIV-1-infected individuals is needed to guide vaccine design and immunization strategies. Here we used a large panel of 44 HIV-1 envelope variants (subtypes A, B, and C) to evaluate the presence of broadly neutralizing antibodies in serum samples obtained 3 years after seroconversion from 40 women enrolled in the CAPRISA 002 acute infection cohort. Seven of 40 participants had serum antibodies that neutralized more than 40% of viruses tested and were considered to have neutralization breadth. Among the samples with breadth, CAP257 serum neutralized 82% (36/44 variants) of the panel, while CAP256 serum neutralized 77% (33/43 variants) of the panel. Analysis of longitudinal samples showed that breadth developed gradually starting from year 2, with the number of viruses neutralized as well as the antibody titer increasing over time. Interestingly, neutralization breadth peaked at 4 years postinfection, with no ...
TY - JOUR. T1 - Formalin-inactivated EV71 vaccine candidate induced cross-neutralizing antibody against subgenotypes B1, B4, B5 and C4A in adult volunteers. AU - Chou, Ai Hsiang. AU - Liu, Chia Chyi. AU - Chang, Jui Yuan. AU - Jiang, Renee. AU - Hsieh, Yi Chin. AU - Tsao, Amanda. AU - Wu, Chien Long. AU - Huang, Ju Lan. AU - Fung, Chang Phone. AU - Hsieh, Szu Min. AU - Wang, Ya Fang. AU - Wang, Jen Ren. AU - Hu, Mei Hua. AU - Chiang, Jen Ron. AU - Su, Ih Jen. AU - Chong, Pele Choi Sing. PY - 2013/11/21. Y1 - 2013/11/21. N2 - Background: Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia. No effective EV71 vaccine is available. A randomized and open-label phase I clinical study registered with ClinicalTrials.gov #NCT01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated EV71 vaccine candidate (EV71vac) at 5- and 10-μg doses. In this study we report the cross-neutralizing ...
Science, 342(6165), 1477-1483. Julien, J. , Taneva, S. , Nieva, J. , et al. (2010). Ablation of the complementarity-determining region H3 apex of the antiHIV-1 broadly neutralizing antibody 2F5 abrogates neutralizing capacity without affecting core epitope binding. Journal of Virology, 84(9), 4136-4147. , et al. (2012). Targeting antibody responses to the membrane proximal external region of the envelope glycoprotein of human immunodeficiency virus. PLoS One, 7(5), e38068. , Matyas, G. , McCutchan, F. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature, 491(7424), 406-412. , et al. (2012). Recognition of membrane-bound fusion-peptide/MPER complexes by the HIV-1 neutralizing 2F5 antibody: Implications for anti-2F5 immunogenicity. PLoS One, 7(12), e52740. , Valpuesta, J. , et al. (2008). The broadly neutralizing ...
Seth, Ankit, Santosh K. Maurya, Ashish Srivastava (2014) Formulation development, characterization and estimation of acid neutralization capacity of shankha bhasma tablets for the treatment of dyspepsia. [Publication] Full text not available from this repository ...
The occurrence of clinical manifestations associated with primary human immunodeficiency virus type 1 (HIV-1) infection was evaluated in a prospective cohort study of female sex workers in Mombasa, Kenya. Among 103 women who seroconverted to HIV-1, fever, vomiting, diarrhea, headache, arthralgia, myalgia, skin rash, swollen lymph nodes, extrainguinal lymphadenopathy, inguinal lymphadenopathy, and vaginal candidiasis were noted significantly more frequently at visits in which seroconversion first became evident. Eighty-one percent of seroconverting women had ≥1 of these 11 symptoms or signs. Among 44% of the women, the acute illness was severe enough to prevent them from working. Having ≥2 of 6 selected symptoms and signs yielded a sensitivity of 51%, specificity of 83%, positive likelihood ratio of 3.2, and negative likelihood ratio of 0.5 for acute HIV-1 infection. The recognition of primary HIV-1-infection illness in high-risk populations and subsequent risk-reduction counseling could ...
Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. We hypothesize that consistent bnAb elicitation will require germline-targeting priming immunogens, to activate bnAb precursor B cells, and structure-guided, or reductionist, boosting immunogens, to shepherd antibody maturation toward bnAb development. To test this hypothesis, we have focused our initial immunogen design work on VRC01- and PGT121-class bnAbs, but we are addressing other bnAb classes as well, because an effective vaccine will likely need to induce multiple bnAbs of complementary specificities. Our efforts to design, evaluate and optimize the immunogens and immunization regimens are iterative, collaborative and multi-disciplinary. Overall, the work in progress represents an attempt to introduce a new way to design vaccines.. ...
A panel of anti-gp120 human monoclonal antibodies (HuMAbs), CD4-IgG, and sera from people infected with human immunodeficiency virus type 1 (HIV-1) was tested for neutralization of nine primary HIV-1 isolates, one molecularly cloned primary strain (JR-CSF), and two strains (IIIB and MN) adapted for growth in transformed T-cell lines. All the viruses were grown in mitogen-stimulated peripheral blood mononuclear cells and were tested for their ability to infect these cells in the presence and absence of the reagents mentioned above. In general, the primary isolates were relatively resistant to neutralization by the MAbs tested, compared with the T-cell line-adapted strains. However, one HuMAb, IgG1b12, was able to neutralize most of the primary isolates at concentrations of | or = 1 microgram/ml. Usually, the inability of a HuMAb to neutralize a primary isolate was not due merely to the absence of the antibody epitope from the virus; the majority of the HuMAbs ...
Human immunodeficiency virus (HIV-1) envelope glycoprotein subunits, such as the gp120 exterior glycoprotein, typically elicit antibodies that neutralize T-cell-line-adapted (TCLA), but not primary, clinical isolates of HIV-1. Here we compare the immunogenicity of gp120 and soluble stabilized trimers, which were designed to resemble the functional envelope glycoprotein oligomers of primary and TCLA HIV-1 strains. For both primary and TCLA virus proteins, soluble stabilized trimers generated neutralizing antibody responses more efficiently than gp120 did. Trimers derived from a primary isolate elicited antibodies that neutralized primary and TCLA HIV-1 strains. By contrast, trimers derived from a TCLA isolate generated antibodies that neutralized only the homologous TCLA virus. Thus, soluble stabilized envelope glycoprotein trimers derived from primary HIV-1 isolates represent defined immunogens capable of eliciting ...
Membrane fusion induced by the envelope glycoprotein enables the intracellular replication of HIV-1; hence, this process constitutes a major target for antiretroviral compounds. It has been proposed that peptides having propensity to interact with membrane interfaces might exert broad antiviral activity against enveloped viruses. To test this hypothesis, in this contribution we have analyzed the antiviral effects of peptides derived from the membrane-proximal external region and the transmembrane domain of the envelope glycoprotein subunit gp41, which display different degrees of interfacial hydrophobicity. Our data support the virucidal activity of a region that combines hydrophobic-at-interface membrane-proximal external region aromatics with hydrophobic residues of the transmembrane domain, and contains the absolutely conserved 679LWYIK/R683 sequence, proposed to embody a cholesterol recognition/interaction amino acid consensus motif. We further sought to correlate the antiviral activity ...
Virologic and immunologic studies were performed on five patients presenting with primary human immunodeficiency virus type 1 (HIV-1) infection. CD8+ cytotoxic T lymphocyte (CTL) precursors specific for cells expressing antigens of HIV-1 Gag, Pol, and Env were detected at or within 3 weeks of presentation in four of the five patients and were detected in all five patients by 3 to 6 months after presentation. The one patient with an absent initial CTL response had prolonged symptoms, persistent viremia, and low CD4+ T-cell count. Neutralizing antibody activity was absent at the time of presentation in all five patients. These findings suggest that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and indicate a role for CTL in protective immunity to HIV-1 in vivo. ...
4LSS: Crystal structure of broadly and potently neutralizing antibody VRC01 in complex with HIV-1 clade A strain KER_2018_11 gp120
A team of NIH scientists has developed a new tool to identify broadly neutralizing antibodies (bNAbs) capable of preventing infection by the majority of HIV strains found around the globe, an advance that could help speed HIV vaccine research. Scientists have long studied HIV-infected individuals whose blood shows powerful neutralization activity because understanding how HIV bNAbs develop and attack the virus can yield clues for HIV vaccine design. But until now, available methods for analyzing blood samples did not easily yield specific information about the HIV bNAbs present or the parts of the virus they targeted. In addition, determining where and how HIV bNAbs bind to the virus has been a laborious process involving several complicated techniques and relatively large quantities of blood from individual donors ...
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Custom polyclonal antibody production, antibodies for cell signaling and signal transduction pathways, cellular organelle markers, 1-month antibody protocol,1-month antibody protocol sicgen,1-month short polyclonal antibody protocol,12-week antibody protocol, 12-week antibody protocol sicgen,12-week classic polyclonal antibody protocol,28-day antibody protocol, 28-day antibody protocol sicgen, 28-day short polyclonal antibody protocol, 3-month antibody protocol, 3-month antibody protocol sicgen, 3-month classic polyclonal antibody protocol, 4-week short polyclonal ...
The recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. ...
The H7N9 viruses have been circulating for six years. The insertion of a polybasic cleavage site in the haemagglutinin (HA) protein of H7N9 has resulted in the emergence of a highly pathogenic (HP) avian influenza virus. Currently, there are limited studies on neutralizing monoclonal antibodies(mAbs) against HP H7N9 AIVs. In this study, mice were immunized with inactivated H7N9 vaccine of A/ZJU01/PR8/2013 to produce murine mAbs. Finally, two murine mAbs against the HA of low pathogenic (LP) virus were produced and characterized. Characterization included determining mAbs binding breadth and affinity, in vitro neutralization capacity, and potential in vivo protection. Two of these mAbs, 1H10 and 2D1, have been identified to have therapeutic and prophylactic efficacy against the HP strain in mouse passive transfer-viral challenge experiments. The mAb 1H10 was most efficacious, even if the treatment-time was as late as 72 h post-infection, or the therapeutic dose was as low as 1 mg/kg; and it ...
Increasing evidence suggests an unexpected potential for non-neutralizing antibodies to prevent HIV infection. Consequently, identification of functional linear B-cell epitopes for HIV are important for developing preventative and therapeutic strategies. We therefore explored the role of antigen-specific immune responses in controlling plasma viremia in SIV infected rhesus macaques. Thirteen rhesus macaques were inoculated either intravaginally or intrarectally with SIVMAC251. Peripheral blood CD4+ T-cells were quantified. Plasma was examined for viremia, antigen specific IgG, IgA and IgM binding responses and neutralizing antibodies. Regions containing binding epitopes for antigen-specific IgG, IgM and IgA responses were determined, and the minimum size of linear Envelope epitope responsible for binding antibodies was identified. The presence of neutralizing antibodies did not correlate the outcome of the disease. In a few SIV-infected macaques, ...
TY - JOUR. T1 - Enhanced HIV type 1 neutralization by human anti-glycoprotein 120 monoclonal antibodies in the presence of monoclonal antibodies to lymphocyte function-associated molecule 1. AU - Hioe, Catarina E.. AU - Hildreth, James. AU - Zolla-Pazner, Susan. PY - 1999/4/10. Y1 - 1999/4/10. N2 - Cellular adhesion receptor LFA-1 and its ICAM ligands are known to play a role in HIV infection. The presence of these molecules on virions and target cells promotes virus infectivity and has previously been shown to hinder virus neutralization by anti-HIV antibodies. To delineate the effect of these molecules on neutralization of HIV-1, human monoclonal antibodies (MAbs) to V3 and the CD4-binding domain (CD4bd) of gp120 were examined in the presence of anti-LFA-1 MAbs. When either of two anti-LFA-1 MAbs was present, higher levels of virus neutralization were achieved by both anti-V3 and anti- CD4bd MAbs. This effect was observed ...
Researchers at The Scripps Research Institute have uncovered the surprising details of how a powerful anti-HIV antibody grabs hold of the virus.
In order to find out if you have been infected with HIV, you need to have a blood test. This blood test, often incorrectly called an AIDS test, is actually a test for HIV antibodies.. Antibodies are produced by your body as a reaction to infection with HIV. An HIV antibody test looks for the presence of these antibodies in your blood. In a standard HIV test, a needle is inserted into a vein in your arm and a sample of your blood is taken. It is sent to a lab to be tested for the presence of these antibodies. After about two weeks, the test results come back to the office where you had the test done.. Rapid HIV tests are available in some regions across the country. The entire process with the new tests, including taking a drop of blood from your finger, along with HIV counselling before and after the test, takes about 20 minutes. The results that you receive from the rapid test are very accurate.. Since HIV antibody tests look for antibodies ...
Interventions to prevent HIV-1 infection and alternative tools in HIV cure therapy remain pressing goals. Recently, numerous broadly neutralizing HIV-1 monoclonal antibodies (bNAbs) have been developed that possess the characteristics necessary for potential prophylactic or therapeutic approaches. However, formulation complexities, especially for multiantibody deliveries, long infusion times, and production issues could limit the use of these bNAbs when deployed, globally affecting their potential application. Here, we describe an approach utilizing synthetic DNA-encoded monoclonal antibodies (dmAbs) for direct in vivo production of prespecified neutralizing activity. We designed 16 different bNAbs as dmAb cassettes and studied their activity in small and large animals. Sera from animals administered dmAbs neutralized multiple HIV-1 isolates with activity similar to that of their parental recombinant mAbs. Delivery of multiple dmAbs to a single animal led to increased ...
The botulinum neurotoxins (BoNTs) are category A biothreat agents which have been the focus of intensive efforts to develop vaccines and antibody-based prophylaxis and treatment. Such approaches must take into account the extensive BoNT sequence variability; the seven BoNT serotypes differ by up to 70% at the amino acid level. Here, we have analyzed 49 complete published sequences of BoNTs and show that all toxins also exhibit variability within serotypes ranging between 2.6 and 31.6%. To determine the impact of such sequence differences on immune recognition, we studied the binding and neutralization capacity of six BoNT serotype A (BoNT/A) monoclonal antibodies (MAbs) to BoNT/A1 and BoNT/A2, which differ by 10% at the amino acid level. While all six MAbs bound BoNT/A1 with high affinity, three of the six MAbs showed a marked reduction in binding affinity of 500- to more than 1,000-fold to BoNT/A2 toxin. Binding results ...
A family of broadly neutralizing antibodies from a chronically infected donor provides a schematic for designing vaccines and treatments that target multiple strains of the virus.. 0 Comments. ...
A family of broadly neutralizing antibodies from a chronically infected donor provides a schematic for designing vaccines and treatments that target multiple strains of the virus.. 0 Comments. ...
Strong maternal antibodies for HIV could be ineffective for protecting infants from HIV. Maternal Anti-HIV Antibodies Associate with Enhanced Transmission.
In this study, we attempted to induce mutations in the MN strain of HIV-1 by subjecting the virus to the immunological selective pressure associated with growth in the presence of human serum with high NA activity directed predominately against the V3 region neutralization determinant. We hypothesized that this selective pressure would result in a mutation(s) in the V3 neutralization determinant itself and that the mutation(s) would result in selective resistance to neutralization by the serum used for the selection process and other sera that reacted selectively with the MN V3 neutralization determinant. The four different NR viruses so derived were found to be broadly resistant to neutralization by all of the human sera that we tested, including some that had NA activity that could not be demonstrated to be directed against the V3 determinant by peptide blocking experiments. Sequencing of the PCR DNA spanning the V3 regions of the four different NR viruses derived by this procedure did not ...
We describe microneutralization assays that used automated 96-well enzyme-linked immunospot (ELI-SPOT) readout instrumentation to measure human anti-dengue virus (DENV) antibodies in CV-1 cells that were stably transfected to express human FcγRIIA (CD32) using conventional Vero cells as a comparator. Classic plaque reduction neutralization test (PRNT) end-point titers were determined by probit analysis. Neutralization titers against DENV measured in CV-1 transfectants were expressed in terms of both conventional 50% to 90% PRNT end-point titers and differential infectivity of antibody-treated virus in control and CD32-expressing CV-1 cells. Significantly reduced PRNT titers and strikingly heightened infectivity (up to 100-fold) of antibody-treated DENV was observed in CV-1 CD32 transfectants compared with that observed in control CV-1 or Vero cells. Because DENVs may preferentially replicate in CD32-expressing monocytes/macrophages and ...
In the absence of truly effective and sustainable vector control measures, a dengue vaccine is urgently needed. While dengue vaccines have been under development since the 1940s, due to the limited appreciation of global dengue disease burden and of the potential markets for dengue vaccines, the industrys interest languished throughout much of the 20th century.. In recent years, however, the development of dengue vaccines has accelerated dramatically. Sanofi Pasteurs Dengvaxia® became the first dengue vaccine to be licensed for use in 2015. Today, several other vaccines are in various stages of advanced development, with clinical trials currently underway.. Vaccine development for dengue is particularly challenging because dengue fever is caused by any of four related, but distinct, virus serotypes (DENV-1-4). While infection by one virus provides lifelong immunity against that serotype, it provides only partial and transient immunity against the other three. This means that an effective ...
HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4⁺ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each ...
The present study is designed as a prospective observational study directed at evaluating the frequency, magnitude, quality and persistence (primary endpoint) of the anti-Tat immune response in HIV-1 infected asymptomatic individuals, and to prospectively evaluate the immunological, virological and clinical outcome of anti-Tat positive versus anti-Tat negative drug naїve subjects (secondary endpoint) in order to determine the impact of anti-Tat immunity on HIV disease progression as well as the potential use of anti-Tat immune response assessment for the clinical and therapeutic management of infected patients. This survey provided important information for the design, planning and conduction of future therapeutic vaccine trials based on the HIV-1 Tat protein in asymptomatic subjects ...
In the past few years, several highly potent, broadly neutralizing antibodies (bNAbs) specific for the gp120 envelope protein of HIV-1 have been discovered. The goal of this work is to use this information to inform the design of vaccines that are able to induce such antibodies (see the Perspective by Crowe). However, because of extensive somatic hypermutation, the epitope bound by these antibodies often does not bind to the germline sequence. Jardine et al. (p. 711, published online 28 March; see the cover) used computational analysis and in vitro screening to design an immunogen that could bind to VRC01-class bNAbs and to their germline precursors. Georgiev et al. (p. 751) took advantage of the fact that only four sites on the HIV viral envelope protein seem to bind bNAbs, and sera that contain particular bNAbs show characteristic patterns of neutralization. An algorithm was developed that could successfully delineate the neutralization specificity of antibodies present in ...
It is currently accepted that a positive Western blot (WB) HIV antibody test is synonymous with HIV infection and the attendant risk of developing and dying from AIDS. In this communication we present a critical evaluation of the presently available data on HIV isolation and antibody testing. The available evidence indicates that: (a) the antibody tests are not standardised; (b) the antibody tests are not reproducible; (c) the WB proteins (bands) which are considered to be coded by the HIV genome and to be specific to HIV may not be coded by the HIV genome and may in fact represent normal cellular proteins; (d) even if the proteins are specific to HIV, because no gold standard has been used and may not even exist to determine specificity, a positive WB may represent nothing more than cross‑reactivity with the many non‑HIV antibodies present in AIDS patients and those at ...
Researchers report a breakthrough in generating powerful antibodies that can neutralize HIV. An HIV infection is really an intensive molecular arms race launched from the minute the virus infects a new host. AIDS progresses not because the body isnt capable of fighting off HIV - it is.
HIV tests that detect HIV antigen (p24) and/or HIV antibody are used to screen for and diagnose HIV infections. Early detection and treatment of HIV infection can decrease the risk of progression to AIDS and greatly improve long-term health and survival.
If it is indeed the case, as the FDA and manufacturers of HIV antibody tests contend, that the significance of a positive Western Blot (WB) in healthy blood donors (or anyone without symptoms of AIDS) is not known, then what...
The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC50). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from ...
Observing the evolution of a particular type of antibody in an infected HIV-1 patient, a study spearheaded by Duke University, including analysis from Los Alamos National Laboratory, has provided insights that will enable vaccination strategies that mimic the actual antibody development within the body. The kind of antibody studied is called a broadly cross-reactive neutralizing antibody, and details of its generation could provide a blueprint for effective vaccination, according to the studys authors. In a paper published online in Nature this week, the team reported on the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The observations trace the co-evolution of the virus and antibodies, ultimately leading to the development of a strain of the potent ...
Antibodies are proteins of the immune system that travel through the bloodstream and recognize potential threats to the body, whether bacteria, viruses or abnormal cells. Most antibodies have a characteristic Y shape. The tips of the Y form a "lock" that binds to a specific "key" carried by foreign bodies that the immune system should destroy.. According to Curiel, recent work by other groups has identified an unusually small and stable class of antibodies made by camels, alpacas and related species collectively classified as camelids. The "lock" of camelid antibodies consists of the stem of the Y only, so it cant unfold in the harsh internal environment of the cell.. "We found that when we incorporated the camelid antibodies into the virus, they retained their binding specificity," Curiel said. "This opens the door to targeting these antibodies to specific tumor markers.". Currently available viral-based cancer therapeutics and those in human trials are not targeted ...
This invention relates to recombinant human monoclonal antibodies which bind to PSMA and related antibody-based compositions aqnd molecules, are disclosed. The human antibodies can be produced in a nonhuman transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, nonhuman transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human ...
TY - JOUR. T1 - Retraction. T2 - Dengue virus envelope protein domain I/II hinge determines long-lived serotype-specific dengue immunity (Proc Natl Acad Sci USA (2014) 111, (1939-1944) DOI: 10.1073/pnas.1317350111). AU - Messer, William. AU - De Alwis, Ruklanthi. AU - Yount, Boyd L.. AU - Royal, Scott R.. AU - Huynh, Jeremy P.. AU - Smith, Scott A.. AU - Crowe, James E.. AU - Doranz, Benjamin J.. AU - Kahle, Kristen M.. AU - Pfaff, Jennifer M.. AU - White, Laura J.. AU - Sariol, Carlos A.. AU - De Silva, Aravinda M.. AU - Baric, Ralph S.. PY - 2015/5/19. Y1 - 2015/5/19. UR - http://www.scopus.com/inward/record.url?scp=84929484676&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84929484676&partnerID=8YFLogxK. U2 - 10.1073/pnas.1506982112. DO - 10.1073/pnas.1506982112. M3 - Article. C2 - 25941397. AN - SCOPUS:84929484676. VL - 112. SP - E2738. JO - Proceedings of the National Academy of Sciences of the United States of America. JF - Proceedings of the National Academy of ...
The isolation of J3 represents a significant improvement on previous nAbs derived from immunized animals as in single-domain VHH form it has a comparable breadth and potency to the best nAbs obtained from a limited number of natural human infections. In contrast, previous nAb clones characterized from immunized animals have only exhibited limited breadth (Forsman et al., 2008; Sundling et al., 2010). A caveat to this is the observation that sera with 17b-like binding specificity can be induced after immunization of humans (Vaine et al., 2010), and it should be noted that 17b and other Abs to CD4-induced epitopes are less broadly neutralizing as full-length mAbs than in Fab form (Labrijn et al., 2003). However, given the previously reported decrease in neutralization ability seen with the Fab of b12 (Labrijn et al., 2003), it appears the CD4-binding site of Env is not per se more easily targeted for neutralization by small Ab fragments as is the CD4-induced ...
Some 25 years after the AIDS epidemic spawned a worldwide search for an effective vaccine against the human immunodeficiency virus, progress in the field seems to have effectively become stalled. The reason? According to new findings, its at least partly due to the fact that our bodys natural HIV antibodies simply dont have a long enough reach to effectively neutralize the viruses they are meant to target.
I thought the HPV vaccine Cervarix would protect me against cervical cancer. I thought I would be armed for life. It only took one injection to find out I was wrong.. My regular week used to consist of a 9-5 work schedule, 2-hour workouts at the gym, 10-kilometer runs during weekdays, long-distance runs on the weekends, and a lot of nights out with out-of-town trips with friends in between.. But all that changed when I decided to have my first shot of Cervarix last September 2013.. Our office was offering Cervarix shots at a subsidized price as part of their Health & Wellness program. Since Cervarix shots are sold at an expensive price here in the Philippines, most of us decided to take advantage of the offer.. The day I got my first shot, my arm hurt a lot but I was told that it was just normal and that the pain would go away after a few days. After around 4 days, the pain did go away and I thought that was the last inconvenience Ill experience because of Cervarix.. But I was wrong.. Less ...
In this animation, professor Cameron Abrams describes a new molecule that hes developed here at Drexel, called DAVEI. DAVEI essentially neutralizes HIV, by tricking the virus into think that its attached to a cell. The virus then spews out its contents, which float off into oblivion, rendering he virus inert.. "We hypothesized that an important role of the fusion machinery is to open the viral membrane when triggered, and it follows that a trigger didnt necessarily have to be a doomed cell," Abrams said. "So we envisioned particular ways the components of the viral fusion machinery work and designed a molecule that would trigger it prematurely," Abrams said.. The team designed DAVEI from two main ingredients. One piece, called the Membrane Proximal External Region (MPER), is itself a small piece of the fusion machinery and interacts strongly with viral membranes. The other piece, called cyanovirin, binds to the sugar coating of the protein spike. Working ...
This experiments aim is to provide students the molecular biology and pathogenesis basics of acquired immunodeficiency syndrome (AIDS).. An HIV test detects HIV infection indirectly using an ELISA test against HIV antibodies in the blood. The test works by taking antibodies from the patients blood and adding them to a microtiter plate coated with HIV antigen. If HIV antibodies are present in the blood, they will bind to the antigens on the plate. This binding is detected with an enzyme-linked secondary antibody that causes a color change upon addition of substrate. In this experiment, students will perform an ELISA test by coating microtiter plate wells with simulated HIV antigen and then test simulated donor serum for anti-HIV antibodies.. , Kit includes: ...
Monoclonal antibodies are a unique class of biological agents that have been developed for autoimmune disease, antitumor and antiplatelet therapy to name a few. Antibodies produced by the body in response to an infection are polyclonal antibodies, meaning the antibodies produced are not identical. Monoclonal antibodies are immunoglobulins that are identical and bind to the same antigenic surface marker, thus the term targeted therapy. The naming of monoclonal antibodies is based on the target of the antibody (e.g. tumor, viral) and the source from which the antibody was produced (e.g. murine, human), followed by the "mab" suffix. While monoclonal antibodies have a wide therapeutic benefit, they have limitations including inability to cross the blood brain barrier and cost.. This presentation will review the history, types and immunogenicity of each type of monoclonal antibody. The nurse will understand the ...
New York, Sep 16 (IANS) In a first study of its magnitude, researchers in the US aim to infuse an antibody into human immunodeficiency virus (HIV)-negative men and transgender individuals to determine whether it will prevent the infection from developing. The Antibody Meditated Prevention (AMP) study - led by an Indian-origin scientist - aims to recruit a combined 2,700 HIV-negative men and transgender individuals whose sexual partners are men - the highest-risk demographic for HIV infection - to test the efficacy of antibody VRC01 in the large clinical trial. "It is the first study of this magnitude to see whether an antibody infusion can help prevent new HIV infections. If it proves effective, it could potentially pave a way for developing a vaccine for HIV infection," said Shobha Swaminathan, an infectious disease specialist from Rutgers University in New Jersey, US.. The ...
A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 is likely to be protective, but this has not been achieved. To explore immunization regimens that might elicit bNAbs, we produced and immunized mice expressing the predicted germline PGT121, a bNAb specific for the V3-loop and surrounding glycans on the HIV-1 spike. Priming with an epitope-modified immunogen designed to activate germline antibody-expressing B cells, followed by ELISA-guided boosting with a sequence of directional immunogens, native-like trimers with decreasing epitope modification, elicited heterologous tier-2-neutralizing responses. In contrast, repeated immunization with the priming immunogen did not. Antibody cloning confirmed elicitation of high levels of somatic mutation and tier-2-neutralizing antibodies resembling the authentic human bNAb. Our data establish that sequential immunization with specifically designed immunogens can induce high ...
A human immunodeficiency virus type 2 (HIV-2)-infected woman experienced asymptomatic superinfection with HIV-1 subtype AG. She did not have cross-neutralizing autologous HIV-1 antibodies before and shortly after HIV-1 superinfection. This evidence supports a mechanism other than cross-neutralizing antibodies for the mild course of HIV-1 infection in this woman.. ...
Custom polyclonal antibody production, antibodies for cell signaling and signal transduction pathways, cellular organelle markers, 1-month antibody protocol,1-month antibody protocol sicgen,1-month short polyclonal antibody protocol,12-week antibody protocol, 12-week antibody protocol sicgen,12-week classic polyclonal antibody protocol,28-day antibody protocol, 28-day antibody protocol sicgen, 28-day short polyclonal antibody protocol, 3-month antibody protocol, 3-month antibody protocol sicgen, 3-month classic polyclonal antibody protocol, 4-week short polyclonal ...
In the past 15-20 years, advances in antibody engineering have facilitated the generation and isolation of monoclonal antibodies (mAbs) to a wide array of antigens. Consequently, mAbs have become essential therapeutic tools and currently dominate the global protein therapeutics market. The engineering of anti-infective antibodies, however, has proven quite a challenge, despite the fact that antibodies were naturally evolved to fight infections. The identification of suitable antigens, the mode of administration and the high cost associated with the production of antibody therapeutics are some of the major hurdles for the progress of anti-infective antibodies. This dissertation addresses issues concerning the development of anti-infective antibodies against two different pathogens: SARS coronavirus (CoV) and two pathogenic species of Burkholderia bacteria. To investigate the role of affinity in viral neutralization and evolution of escape ...
DESCRIPTION (provided by applicant): The HIV-1 epidemic has resulted in ~2.7 million new infections in 2007 for a total of ~33 million people living with HIV/AIDS. Clinical trials have shown that HIV-1 infection cannot be prevented by immunization with monomeric recombinant forms of viral envelope (Env) proteins. However, it is clear that the HIV-1 Env contains epitopes that can induce neutralizing antibodies and that such antibodies can protect primates from infection. The HIV-1 Env is a transmembrane glycoprotein. Both the external subunit (gp120) and the membrane- proximal external region of Env (located within the gp41 subunit) contain epitopes that are the target of broadly neutralizing monoclonal antibodies (mAbs) isolated from infected patients. Considerable effort has been devoted to creating soluble forms of the Env trimer. The improvements in immunogenicity of these molecules relative to monomeric gp120 are limited at best. Another ...
To evaluate the safety of HIV-1 gp120 C4-V3 hybrid polyvalent peptide immunogen (C4-V3 peptides) formulated in mineral oil containing mannose mono-oleate (IFA) in HIV-1 uninfected volunteers. To evaluate the humoral and cellular immune responses to the C4-V3 peptides as measured by the induction of 1 or more of the following: neutralizing antibodies to HIV-1 MN and RF, cross-neutralizing antibodies to primary isolates of HIV-1, HIV-1 antigen-specific lymphoproliferation, CD8+ and CD4+ cytotoxic T lymphocyte (CTL) activity specific for HIV-1 gp120 or V3 peptides corresponding to the vaccine strains of HIV-1, induction of HLA-B7 and HLA-A2 restricted CD8+CTLs, and induction of HIV-specific DTH responses.. The test immunogen (C4-V3 peptides) is constructed from 4 sequences of the HIV-1 V3 gp120 loop shared by approximately 80% of North American HIV-1 strains. Because of the critical role that this region plays in generating anti-HIV sequences, it is ...
... cause of arboviral diseases in humans. on polyclonal sera and B-cells following natural DENV contamination has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV precursor and envelope membrane protein, two surface protein involved with vaccine development, pursuing natural infections; analyses of the discoveries have supplied valuable understanding into brand-new strategies concerning molecular technology to induce stronger neutralizing antibodies and much less BGJ398 ic50 improving antibodies for next-generation dengue vaccine advancement. of the family members 30 CrR (45%)7 ND55425253DIII: lr, str A and str G15 solid NT mAbs14 anti-DIIIShrestha et al., 2010DENV23320 TS (61%)11 CrR (33%)2 ND8621115DIII: lr, CCL and str A, DI: lr,DII: lr, di and FL24 solid NT mAbs11 anti-DIII, 13 ...
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Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA), for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in ...
( i (male) received oral sex on penis and i have herpes 2...What is a HIV Antibody Test w/Reflex .... i have a test in a laboratory but not that kind of test is...i took my hiv antibody test at 8...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
Twenty-five monoclonal antibodies were generated by immunizing mice. Of these, the one named R10 had the strongest neutralizing activity against HAV [a 50% neutralizing concentration (neut50) value of ∼2 nM, ∼0.3 μg/mL]. The Fab fragment is also strongly neutralizing (neut50 = ∼3 nM, ∼0.45 μg/mL) (Fig. 1A). R10 does not recognize linear epitopes by immunoblot, but recognizes conformational epitopes by ELISA, and shows similar binding affinities to full and empty particles (Fig. 1B). Interestingly, a fluorescent assay revealed that whereas the R10 Fab portion destabilizes full HAV particles by 7 °C, the intact R10 stabilizes the particles by 2 °C (Fig. 1C and Fig. S1A). The same assay indicates that the bivalent intact antibody induces a two-stage transition in protein conformation to release the RNA genome (Fig. 1C and Fig. S1A). The first event, producing a slight exposure of RNA, occurs at a similar temperature to that seen with the Fab, whereas the ...
The high overall genetic homology between humans and rhesus macaques, coupled with the phenotypic conservation of lymphocyte populations, highlights the potential use of nonhuman primates (NHPs) for the preclinical evaluation of vaccine candidates. For HIV-1, experimental models are needed to identify vaccine regimens capable of eliciting desired immune responses, such as broadly neutralizing antibodies (bNAbs). One important neutralization target on the HIV-1 envelope glycoproteins (Envs) is the conserved primary CD4 receptor binding site (CD4bs). The isolation and characterization of CD4bs-specific neutralizing monoclonal Abs (mAbs) from HIV-1-infected individuals have provided insights into how broadly reactive Abs target this conserved epitope. In contrast, and for reasons that are not understood, current Env immunogens elicit CD4bs-directed Abs with limited neutralization breadth. To facilitate the use of the NHP model to address this and other questions relevant to human humoral ...
For the study, Prof. Simmons and colleagues studied 145 anti-dengue antibodies from patients infected with dengue virus. They found a new class of antibody that can recognize and bind to a unique structure - known as an epitope - that is present in all four types of dengue virus.. The authors describe the previously unknown epitope as an envelope dimer epitope (EDE) that "bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion.". The antibodies to the epitope were "broadly reactive" across the dengue serotypes and "fully neutralized virus produced in either insect cells or primary human cells," they note.. The findings should clear the way for vaccine trials "in which the induction of antibody to the EDE should be prioritized," they conclude.. In July 2014, Medical News Today reported promising results of the first dengue vaccine widely tested in humans. Reported in The Lancet, the phase 3 clinical ...
The Antibody Resource Page (http://www.antibodyresource.com/) is an invaluable website to researchers and educators. Here is just some of what can be found on the page: 1. How to Find an Antibody - a variety of ways on and off the web to find the antibody you are looking for. There are links to free search engines that allow you to search a multitude of companies for the specific antibody you need. 2. Online Companies - links to over 110 companies that sell antibodies or antibody related products. Is your company listed on this page? 3. Antibody Image Gallery - animated antibody pictures are available 4. Bulletin Board - Have a question? Then stop by and post a message. 5. Educational Resources - a variety of new links have been added.There ...
A protective vaccine against HIV will likely require elicitation of broadly neutralizing antibodies that neutralize a diverse array of HIV strains. Four broadly-neutralizing antibodies are known at present, each targeting a different conserved epitope on the virus. In this project, we focus on the broadly-neutralizing antibody 2F5 that targets an epitope in the membrane-proximal external region of HIV gp41. The project focuses on design of immunogens to re-elicit 2F5-like neutralizing responses, and on redesign of 2F5 itself to improve our understanding of its mechanism of neutralization. Both aims will employ a combination of computational design and directed evolution.. Aim 1: Develop novel membrane-protein based immunogens that conformationally stabilize the 2F5 epitope in the context of a lipid membrane to best approximate the epitope environment on the virion.. Aim 2: Design and characterize variants of the 2F5 antibody ...
Extensive shielding by N-glycans on the surface of the HIV envelope glycoproteins (Env) restricts B cell recognition of conserved neutralizing determinants. Elicitation of broadly neutralizing antibodies (bNAbs) in selected HIV-infected individuals reveals that Abs capable of penetrating the glycan shield can be generated by the B cell repertoire. Accordingly, we sought to determine if targeted N-glycan deletion might alter antibody responses to Env. We focused on the conserved CD4 binding site (CD4bs) since this is a known neutralizing determinant that is devoid of glycosylation to allow CD4 receptor engagement, but is ringed by surrounding N-glycans. We selectively deleted potential N-glycan sites (PNGS) proximal to the CD4bs on well-ordered clade C 16055 native flexibly linked (NFL) trimers to potentially increase recognition by naïve B cells in vivo. We generated glycan-deleted trimer variants that maintained native-like conformation and ...
The design of a human immunodeficiency virus-1 (HIV-1) immunogen that can induce broadly reactive neutralizing antibodies is a major goal of HIV-1 vaccine development. Although rare human monoclonal antibodies (mAbs) exist that broadly neutralize HIV-1, HIV-1 envelope immunogens do not induce these antibody specificities. Here we demonstrate that the two most broadly reactive HIV-1 envelope gp41 human mAbs, 2F5 and 4E10, are polyspecific autoantibodies reactive with the phospholipid cardiolipin. Thus, current HIV-1 vaccines may not induce these types of antibodies because of autoantigen mimicry of the conserved membrane-proximal epitopes of the virus. These results may have important implications for generating effective neutralizing antibody responses by using HIV-1 vaccines.. ...
No licensed vaccine is available for prevention of EBV-associated diseases, and robust, sensitive, and high-throughput bioanalytical assays are needed to evaluate immunogenicity of gp350 subunit-based candidate EBV vaccines. Here we have developed and improved analytical tools for such a vaccines pre-clinical and clinical validation including a gp350-specific antibody detection assay and an EBV-GFP based neutralization assay for measuring EBV specific antibodies in human donors. The sensitivity of our previously published high-throughput EBV-GFP fluorescent focus (FFA)-based neutralization assay was further improved when guinea pig complement was supplemented using a panel of healthy human sera. Anti-gp350 antibody titers, which were evaluated using an anti-gp350 IgG ELISA assay optimized for capture and detection conditions, were moderately correlated to the FFA-based ...
High performance of the K2 summit camera gives higher contrast, which is extremely helpful when studying heterogeneous particles. Shown above are 4 different populations of particles, which are found when mixing the HIV-1 envelope glycoprotein trimer with the antigen binding region of an anti-HIV antibody helping to guide rational vaccine development ...
Alberini, Isabella, Del Tordello, Elena, Fasolo, Alba, Temperton, Nigel J., Galli, Grazia, Gentile, Chiara, Montomoli, Emanuele, Hilbert, Anne K., Banzhoff, Angelika, Del Giudice, Giuseppe, Donnelly, John J., Rappuoli, Rino and Capecchi, Barbara (2009) Pseudoparticle neutralization is a reliable assay to measure immunity and cross-reactivity to H5N1 influenza viruses. Vaccine, 27 (43). pp. 5998-6003. ISSN 0264-410X (doi:10.1016/j.vaccine.2009.07.079) Ascione, Alessandro, Capecchi, Barbara, Campitelli, Laura, Imperiale, Valentina, Flegoa, Michela, Zamboni, Silvia, Gellini, Mara, Alberini, Isabella, Pittiglio, Eliana, Donatelli, Isabella, Temperton, Nigel J. and Cianfriglia, Maurizio (2009) Human monoclonal antibodies in single chain fragment variable format with potent neutralization activity against influenza virus H5N1. Antiviral Research, 83 (3). pp. 238-244. ISSN 0166-3542 (doi:10.1016/j.antiviral.2009.05.005) Oha, Sawyin, Selleck, Paul, Temperton, Nigel J., Chan, Paul K.S., Capecchi, ...
A new study has shown that infusion of a broadly neutralizing antibody VRC01 in virally suppressed, early treated volunteers was associated with a modestly delayed rebound of HIV after interruption of antiretroviral therapy.
An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.
Rusert, P; Krarup, A; Magnus, C; Brandenberg, O F; Weber, J; Ehlert, A K; Regoes, R R; Günthard, H F; Trkola, A (2011). Interaction of the gp120 V1V2 loop with a neighboring gp120 unit shields the HIV envelope trimer against cross-neutralizing antibodies. Journal of Experimental Medicine, 208(7):1419-1433.. Ruprecht, C R; Krarup, A; Reynell, L; Mann, A M; Brandenberg, O F; Berlinger, L; Abela, I A; Regoes, R R; Günthard, H F; Rusert, P; Trkola, A (2011). MPER-specific antibodies induce gp120 shedding and irreversibly neutralize HIV-1. Journal of Experimental Medicine, 208(3):439-454.. Pugach, P; Krarup, A; Gettie, A; Kuroda, M; Blanchard, J; Piatak Jr, M; Lifson, J D; Trkola, A; Robbiani, M (2010). In vivo binding and retention of CD4-specific DARPin 57.2 in macaques. PLoS ONE, 5(8):e12455.. ...
Significant efforts have been made to identify HIV-1 neutralizing antibodies because they are considered to be critical to the design of an effective HIV-1 vaccine. proteins. Keywords: HIV-1, Surface-expressed envelope trimer, Single B cell sort, HIV-1 neutralizing Antibodies 1 Introduction Broadly neutralizing antibodies (bNAbs) targeting HIV-1 can prevent infection in non-human primates, and control HIV-1 replication in humanized mice (Mascola et al., 2000; Hessell et al., 2009; Klein et al., 2012b). These antibodies are therefore of significant interest for vaccine design and as agents for novel therapeutic approaches (McCoy and Weiss, 2013). Given their potential importance, substantial efforts have been made to dissect the human anti-HIV-1 antibody response in individuals who display broad and potent HIV-1 serum neutralizing activity (McCoy and Weiss, 2013). An essential component to this effort has been the development of new methods for ...
Scientists have isolated the most powerful broadly neutralizing antibodies (bNAbs) against HIV so far - a major step towards finding an effective vaccine against the deadly virus. Capable of fighting a broad spectrum of variants of HIV, the virus that causes AIDS, some of the 17 antibodies discovered jointly by The International AIDS Vaccine Initiative (IAVI) and The Scripps Research Institute blocked HIV infection of cells as much as 10 to 100 times as potently as the previously discovered bNAbs. These HIV neutralizing antibodies are produced naturally by a minority infected with HIV, but who show no symptoms ...
According to a recent study, observing the evolution of a particular type of antibody in an infected HIV-1 patient has provided insights that will enable vaccination strategies that mimic the actual antibody development within the body.
Significant efforts have been made to identify HIV-1 neutralizing antibodies because they are considered to be critical to the design of an effective HIV-1 vaccine. proteins. Keywords: HIV-1, Surface-expressed envelope trimer, Single B cell sort, HIV-1 neutralizing Antibodies 1 Introduction Broadly neutralizing antibodies (bNAbs) targeting HIV-1 can prevent infection in non-human primates, and control HIV-1 replication in humanized mice (Mascola et al., 2000; Hessell et al., 2009; Klein et al., 2012b). These antibodies are therefore of significant interest for vaccine design and as agents for novel therapeutic approaches (McCoy and Weiss, 2013). Given their potential importance, substantial efforts have been made to dissect the human anti-HIV-1 antibody response in individuals who display broad and potent HIV-1 serum neutralizing activity (McCoy and Weiss, 2013). An essential component to this effort has been the development of new methods for ...
The antibody response is crucial for preventing many viral infections and may also contribute to resolution of infection. When a vertebrate is infected with a virus, antibodies are produced against many epitopes on multiple virus proteins. A subset of these antibodies can block virus infection by a process that is called neutralization. Antibodies can neutralize viral infectivity…
CDC scientists identified a partner for a Cooperative Research and Development Agreement, Trellis Bioscience, to collaborate on additional studies to prove the viability of the antibodies directed against the G protein as potential therapeutic antibodies against RSV. Together, scientists at CDC and Trellis identified high-affinity fully human antibodies that mimicked the mouse monoclonal antibodies in in vitro assays and mouse models. Based on the positive results obtained during the collaboration, Trellis obtained an exclusive patent license to take these RSV anti-G antibodies into human trials, and bring to market a commercial product that shows improved safety and efficacy over currently available antibodies. These RSV anti-G antibodies have the potential to dramatically decrease the number of hospitalizations and deaths of infants, children, and the elderly due to respiratory tract disease caused by RSV infection ...
ml, 1 mg, 1, 100 µg CCR8 Antibody 1 mg, 6 Antibody (Monoclonal, pro) Antibody (Monoclonal, 50 µg PAX7 Antibody 1 mg, 100 µg EHMT2 Antibody (Monoclonal, 100 µg FXR Antibody (Monoclonal, 100 µg RXRA Antibody (Monoclonal
A vital step in HIV vaccine development strategies has been the observation that some infected individuals generate broadly neutralizing antibodies that target the glycans on the surface of HIV-1 gp120. These antibodies target glycan epitopes on viral envelope spikes and yet the positions and degree of occupancy of glycosyla-tion sites is diverse. Therefore, there is a need to understand glycosylation occupancy on recombinant immunogens. The sheer number of potential glycosylation sites and degree of chemical heterogeneity impedes assessing the global sequon occupancy of gp120 glycoforms.. For this publication we trapped the glycan processing of recombinant gp120 to generate homogenous glycoforms, to facilitate the occupancy assessment by intact mass spectrometry. We show that gp120 monomers of the BG505 strain contain either a fully occupied sequenz or miss one and sometimes two glycans across the ...
DESCRIPTION (provided by applicant): 4E10 is a monoclonal antibody that was derived from the B cells of a patient with persistent HIV infections. In vitro and in vivo, 4E10 neutralizes a wide variety of HIV and SHIV strains. As such, an immunogen that elicits 4E10-like antibody responses in humans would be a huge advance toward the goal of designing a safe and effective vaccine against HIV. Although the epitope for 4E10 was found to be a six amino acid peptide (NWFNIT) from the fusogenic domain of gp41, attempts to use this peptide as an immunogen to elicit antibodies that mimic the HIV neutralizing activity of 4E10 have been totally unsuccessful. This result indicates that antigen presentation is possibly the missing link that lies between immunization with NWFNIT-containing immunogens and the successful elicitation of 4E10-like antibodies in vivo. For over a decade we have been developing methods in peptide chemistry to ...
Researchers have traced in detail how certain powerful HIV neutralizing antibodies evolve, a finding that generates vital clues to guide the design of a preventive HIV vaccine, according
Background:. Despite the introduction of highly effective antiretroviral therapy (ART) regimes, which control the HIV infection and results in increases in CD4 cell counts and an undetectable viral load, many patients suffer from increased morbidity. There is evidence that presence of antibodies against the C5 region of gp120 strongly correlates with slower disease progression, and that loss of antibody responses to this region are associated with progression.. Investigational product:. Vacc-C5 is a single heterodimeric peptide-based HIV therapeutic vaccine corresponding to the C5 region on gp120 and the external domain of gp41. The vaccine is intended to create a non-neutralizing antibody against C5 region.. Study objectives:. ...
2F5B: Crystallographic definition of the epitope promiscuity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5: vaccine design implications.
1TJI: Structure and mechanistic analysis of the Anti-Human Immunodeficiency Virus type 1 antibody 2F5 in complex with its gp41 epitope
The effects of somatic hypermutation on neutralization and binding in the PGT121 family of broadly neutralizing HIV antibodies. Devin Sok*, Uri Laserson*, Jonathan Laserson*, Yi Liu*, Francois Vigneault, Jean-Philippe Julien, Bryan Briney, Alejandra Ramos, Karen F Saye, Khoa Le, Alison Mahan, Shenshen Wang, Mehran Kardar, Gur Yaari, Laura M Walker, Birgitte B Simen, Elizabeth P St John, Po-Ying Chan-Hui, Kristine Swiderek, Stephen H Kleinstein, Galit Alter, Michael S Seaman, Arup K Chakraborty, Daphne Koller, Ian A Wilson, George M Church, Dennis R Burton, Pascal Poignard. PLoS Pathogens 2013. doi:10.1371/journal.ppat.1003754 , pdf. ...
Scientists at Duke Medicine have found an immunologic mechanism that makes broadly neutralizing antibodies in people who are HIV-1 infected.
In a finding that may be good news for scientists developing HIV vaccines and therapies, a team of researchers at The Rockefeller University and the Howard Hughes Medical Institute have found a way to investigate the broadly ...
Rabbit Polyclonal Anti-MCCC1 Antibody. From world top supplier Cusabio Biotech, validated in ELISA,WB,IHC. AntibodyPlus provides CSB-PA853497ESR2HU trial size antibody samples for antibody validation. Replacement to Santa Cruz, cheaper than Abcam, Sigma and CST antibody.
Rabbit Polyclonal Anti-SOCS4 Antibody. From world top supplier Cusabio Biotech, validated in ELISA,WB,IHC. AntibodyPlus provides CSB-PA022393ESR1HU trial size antibody samples for antibody validation. Replacement to Santa Cruz, cheaper than Abcam, Sigma and CST antibody.
Since antibodies are only produced after exposure to foreign material including organisms such as bacteria and viruses, they indicate exposure to that organism.. Because antibodies remain in circulation for quite some time, the presence of an antibody titre to a particular organism does not necessarily mean that that organism is the cause of the illness that your pet is experiencing.. The lack of an antibody titre to an organism can indicate either of two things. The first is that no exposure to that organism has occurred and therefore your pets current clinical condition is due to another cause. The other is that your pet has been so recently exposed to the organism that there has been insufficient time for antibodies to be produced in sufficient quantities to be detectable in the serum.. Therefore if we suspect that a particular disease (for example leptospirosis) is causing illness in your pet, it is important to obtain both acute and ...
Giving monkeys two powerful anti-HIV antibodies immediately after infection with an HIV-like virus enabled the immune systems of some of the animals to ...

Frontiers | Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds | ImmunologyFrontiers | Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds | Immunology

Promisingly, Fc antigen binding fragment [Fcab] and monomeric antibody or half antibody may be particularly advantageous to ... focuses on the progress of Fc engineering in generating bispecific molecules and on the use of small antibody fragment as ... Promisingly, Fc antigen binding fragment [Fcab] and monomeric antibody or half antibody may be particularly advantageous to ... to antibody fragments. Impressively, antibody fragments such as bispecific T-cell engager [BiTE], bispecific killer cell ...
more infohttps://www.frontiersin.org/articles/10.3389/fimmu.2017.00038/full

Enhanced HIV-1 neutralization by antibody heteroligation | PNASEnhanced HIV-1 neutralization by antibody heteroligation | PNAS

A) Schematic diagram shows the gp120/41 BiAbs made as scFv2-Fc IgG-like molecules bearing one antibody binding site to gp120 ... Antibody 10-188 binds to a linear epitope in the variable loop V3 (gp120V3) (59), and the other two anti-gp120 antibodies ... 2003) Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on ... For the analysis of the simultaneous binding of the anti-gp120/41 BiAb molecules to gp120 binding (binding 1) and to gp41 ( ...
more infohttps://www.pnas.org/content/109/3/875

Human Immunodeficiency Virus (HIV) Separation and Enrichment via the Combination of Antiviral Lectin Recognition and a...Human Immunodeficiency Virus (HIV) Separation and Enrichment via the Combination of Antiviral Lectin Recognition and a...

Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary ... The potent anti-HIV protein cyanovirin-N contains two novel carbohydrate binding sites that selectively bind to man(8) D1D3 and ... Tajima N, Takai M, Ishihara K. Significance of antibody orientation unraveled: well-oriented antibodies recorded high binding ... implications for binding to the HIV envelope protein gp120. J Am Chem Soc. 2001;123(17):3892-902.CrossRefPubMedGoogle Scholar ...
more infohttps://link.springer.com/article/10.1007%2Fs11095-016-1980-7

Common Tolerance Mechanisms, but Distinct Cross-Reactivities Associated with gp41 and Lipids, Limit Production of HIV-1 Broad...Common Tolerance Mechanisms, but Distinct Cross-Reactivities Associated with gp41 and Lipids, Limit Production of HIV-1 Broad...

Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary ... in initial autoantigen-binding assays, exhibited a different spectrum of cross-reactivities (25): for example, 4E10 bound HIV-1 ... HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Nature 420: 678-682. ... Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding. ...
more infohttp://www.jimmunol.org/content/191/3/1260?ijkey=ab4e2438bbfc8c0227af668137a0ec8c452f5bfb&keytype2=tf_ipsecsha

Antibody-Dependent, FcγRI-Mediated Neutralization of HIV-1 in TZM-bl Cells Occurs Independently of Phagocytosis | Journal of...Antibody-Dependent, FcγRI-Mediated Neutralization of HIV-1 in TZM-bl Cells Occurs Independently of Phagocytosis | Journal of...

Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary ... Many cells of the immune system express Fc receptors that bind immune complexes through the constant region of immunoglobulins ... Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120. J. Immunol. 150:635-643. ... We also show that FcγRI occasionally potentiates neutralization by antibodies against the V3 loop of gp120 and cluster I of ...
more infohttps://jvi.asm.org/content/87/9/5287.long

Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41...Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41...

Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary ... Exclusive 2F5-bound face of gp41.In general, antibodies that bind to peptides envelop them, whereas antibodies that bind to ... suggests that unlike anti-gp120 broadly neutralizing antibodies, which bind to disparate regions of gp120, these antibodies may ... Flow cytometry analysis of antibody binding.Anti-HA antibody sc-7392 (Santa Cruz), antibody b12 (D. Burton), and the broadly ...
more infohttps://jvi.asm.org/content/78/19/10724?ijkey=0b90d4470c9f469acac24caecd3c7e870e6ef978&keytype2=tf_ipsecsha

Env (gene) - WikipediaEnv (gene) - Wikipedia

"Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary ... It is originally buried within the viral envelope, but when gp120 binds to a CD4 receptor, gp120 changes its conformation ... Prior to binding the host cell, gp120 remains effectively hidden from antibodies because it is buried in the protein and ... Since CD4 receptor binding is the most obvious step in HIV infection, gp120 was among the first targets of HIV vaccine research ...
more infohttps://en.wikipedia.org/wiki/Env_(gene)

Antibody vs. HIV in a clash of evolutionary titans | PNASAntibody vs. HIV in a clash of evolutionary titans | PNAS

... on the target cell membrane engages the CD4bs on gp120 molecules to assemble and expose the coreceptor binding site. In the ... The conserved coreceptor site is largely inaccessible on monomeric gp120 unless CD4 binds and triggers conformational changes ... b12: An Antibody That Recognizes the CD4 Binding Site of gp120. *Antibodies That Recognize the Coreceptor Binding Site on gp120 ... Antibodies That Recognize the Coreceptor Binding Site on gp120 [CD4-Induced (CD4i) Antibodies]. During infection, the ...
more infohttps://www.pnas.org/content/102/42/14943

Limitations to the Structure-Based Design of HIV-1 Vaccine Immunogens | Springer for Research & DevelopmentLimitations to the Structure-Based Design of HIV-1 Vaccine Immunogens | Springer for Research & Development

Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary ... Mimicking the structure of the V3 epitope bound to HIV-1 neutralizing antibodies. Biochemistry. 2009;48:3288-303.PubMed ... Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat Med. 2007;13:1032-4.PubMedPubMedCentralCrossRefGoogle ... Dissociation rate of antibody-gp120 binding interactions is predictive of V3-mediated neutralization of HIV-1. J Immunol. 1994; ...
more infohttps://rd.springer.com/chapter/10.1007%2F978-3-030-32459-9_12

Patents filed at Aug 22 2017 | Heterodimeric Fc regions, binding molecules comprising same, and methods
     relating thereto |...Patents filed at Aug 22 2017 | Heterodimeric Fc regions, binding molecules comprising same, and methods relating thereto |...

Binding molecules against Chikungunya virus and uses thereof , Neutralizing antibodies to HIV-1 and their use , Antibodies with ... Monoclonal antibodies specific for Cry1Ca and related detection methods , ... Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal ... Binding molecules against Chikungunya virus and uses thereof. The invention relates to binding molecules against Chikungunya ...
more infohttp://www.patents.com/isd-20170822-p68.html

Making Antibodies That Neutralize HIV | National Institutes of Health (NIH)Making Antibodies That Neutralize HIV | National Institutes of Health (NIH)

Researchers have traced in detail how certain powerful HIV neutralizing antibodies evolve, providing vital clues to guide the ... They attach to a molecule called gp120 in a region known as the CD4 binding site. HIV uses this site to attach to the cells it ... Making Antibodies That Neutralize HIV. Illustration showing, in green, where the mature VRC01antibody binds to gp120 (red) on ... Structural analysis revealed that the VRC01-like antibodies from the different donors all bind in the same way to the same spot ...
more infohttps://www.nih.gov/news-events/nih-research-matters/making-antibodies-neutralize-hiv

HIV Vaccine: Recent Advances, Current Roadblocks, and Future DirectionsHIV Vaccine: Recent Advances, Current Roadblocks, and Future Directions

... and V3 on gp120; and binding sites on gp41 molecules such as conserved helices and membrane-proximal external region (MPER) of ... study also found that a cocrystal bound structure of CH103 bnAbs and gp120 produced increased affinity for CD4 binding site and ... and lost the gp120 Asn 332 glycan in both of the antibody treated animals rendering the virus resistant to both the antibody ... V1/V2 region of gp120 interacts with CD4 receptors as well as gut mucosal homing integrin binding site α4β7 of CC chemokine ...
more infohttps://www.hindawi.com/journals/jir/2015/560347/

GPI-anchored single chain Fv - an effective way to capture transiently-exposed neutralization epitopes on HIV-1 envelope spike ...GPI-anchored single chain Fv - an effective way to capture transiently-exposed neutralization epitopes on HIV-1 envelope spike ...

Thus GPI-anchored scFv could be used as a general and effective way to identify antibodies that react with transiently-exposed ... In this study, we constructed single chain Fvs (scFvs) derived from seven human monoclonal antibodies and genetically linked ... epitopes identified so far are present on the surface of native HIV-1 envelope spikes whose recognition by antibodies does not ... Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary ...
more infohttps://retrovirology.biomedcentral.com/articles/10.1186/1742-4690-7-79

Aggregate complexes of HIV-1 induced by multimeric antibodies | Retrovirology | Full TextAggregate complexes of HIV-1 induced by multimeric antibodies | Retrovirology | Full Text

... however little is known about the antibody characteristics required to induce HIV aggregation. Such knowledge may be critical ... Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, ... while b12 binds to CD4 binding site in gp120. To ensure that class switching of these antibodies did not alter their affinity ... These results reflect the ability of antibodies to bind and opsonize virions, but indicate that each arm of an IgG molecule was ...
more infohttps://retrovirology.biomedcentral.com/articles/10.1186/s12977-014-0078-8

Graphical Abstract  Angew. Chem. Int. Ed. 82007Graphical Abstract Angew. Chem. Int. Ed. 82007

Polyclonal antisera against such a mimetic molecule specifically recognize gp120 and compete with mAb b12 for binding to gp120 ... The epitope of the broadly neutralizing anti-HIV-1 antibody mAb b12 overlaps the CD4 binding site (CD4bs) of the viral envelope ... KGaA, Weinheim which prevents the release of unwanted, nonspecifically bound proteins, can be used for a very mild and highly ... R. Franke, T. Hirsch, H. Overwin, J. Eichler* 1253 - 1255 Synthetic Mimetics of the CD4 Binding Site of HIV-1 gp120 for the ...
more infohttps://www.docme.ru/doc/1936374/graphical-abstract--angew.-chem.-int.-ed.-82007

Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal...Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal...

... the coreceptor binding site (CD4i), and other undefined epitopes within gp120. The inability to adsorb cross-neutralizing ... The eluted antibodies were serially diluted and added to the plate for 1 h at 37°C. The bound IgG was detected using a total ... some of these antibodies recognize epitopes only apparent in the context of the trimeric glycoprotein or on the gp41 molecule ( ... broadly cross-neutralizing antibodies have been mapped to the CD4 binding site, ...
more infohttp://pubmedcentralcanada.ca/pmcc/articles/PMC2772769/

Antibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition | ScienceAntibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition | Science

Alanine substitution of many primary combining site residues abolished 2G12 binding to gp120JR-FL. Mutations in sites believed ... A C-type lectin, DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin) also binds ... distinct binding sites for carbohydrate: two correspond to the normal antibody combining site and two to novel sites within the ... of many of the residues involved in binding the D2 arm of Man9GlcNAc2 in the secondary binding site decreased gp120 binding and ...
more infohttp://science.sciencemag.org/content/300/5628/2065?ijkey=e4ece13a2ab9e4f3be93e091b098622b85849ef1&keytype2=tf_ipsecsha

Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization | JEMPotent and broad neutralization of HIV-1 by a llama antibody elicited by immunization | JEM

Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gp120 is sterically restricted on primary ... J3 binds to immunogen HIV Env trimers and competes for the CD4-binding site. J3 binding specificities were examined in ELISA ( ... CD4 as confirmed by the loss of binding seen with the CD4-binding site D368R Gp120YU2 mutant relative to wild-type Gp120YU2. In ... Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat. Med. 13:1032-1034. doi:10.1038/nm1624. ...
more infohttp://jem.rupress.org/content/early/2012/05/22/jem.20112655

Abzyme - WikipediaAbzyme - Wikipedia

If an antibody is developed to bind to a molecule thats structurally and electronically similar to the transition state of a ... at Houston announced that they have engineered an abzyme that degrades the superantigenic region of the gp120 CD4 binding site ... The abzyme does more than bind to the site, it catalytically destroys the site, rendering the virus inert, and then can attack ... By raising an antibody to bind to a stable transition-state analog, a new and unique type of enzyme is produced. So far, all ...
more infohttps://en.wikipedia.org/wiki/Abzyme

Passive transfer of neutralizing individual antibodies against HIV-1 protects macaques against | Selectivity by Small-Molecule...Passive transfer of neutralizing individual antibodies against HIV-1 protects macaques against | Selectivity by Small-Molecule...

... as well as the various other two anti-gp120 antibodies acknowledge conformational epitopes in the Compact disc4 binding site ( ... Antibody 10-188 binds to a linear epitope in the adjustable loop V3 (gp120V3) (59), ... three different individual anti-gp120 antibodies with humble neutralizing activity and one anti-gp41 antibody without ... and Compact disc4-induced coreceptor binding site (Compact disc4i) (1-863 and 4-42, respectively) (Desk S1) (60). Anti-gp120 ...
more infohttp://plant-finder.com/passive-transfer-of-neutralizing-individual-antibodies-against-hiv-1-protects-macaques-against/

anti-CD4 Antikörper (Extracellular Domain) (Biotin) | Produkt Nr. ABIN4260944anti-CD4 Antikörper (Extracellular Domain) (Biotin) | Produkt Nr. ABIN4260944

Mt310 binds to the extracellular domain D1 of CD4 - the same site as the HIV-1 gp120-binding site ... CD4 Antikörper (CD4 Molecule) (Extracellular Domain) (Biotin). Details for Product anti-CD4 Antibody No. ABIN4260944, Anbieter ... The antibodies are intended for use in vitro experiments only. Our antibodies have not been tested nor are recommended for use ... You are viewing an incomplete version of our website. Please click here. to reload the website as full version. ...
more infohttps://www.antikoerper-online.de/antibody/4260944/anti-CD4+Molecule+CD4+Extracellular+Domain+antibody+Biotin/

NEUTRALIZING ANTIBODIES TO HIV-1 AND THEIR USE - Patent applicationNEUTRALIZING ANTIBODIES TO HIV-1 AND THEIR USE - Patent application

... binds to the CD4 binding site of gp120 by partially mimicking the structure of the HIV-1 receptor molecule CD4. Several ... antibody that binds gp120 (the first antibody) is unlabeled and a second antibody or other molecule that can bind the antibody ... 0120] CD4 binding site (CD4BS) antibodies: Antibodies that bind to or substantially overlap the CD4 binding surface of a gp120 ... 33B). The VRC13 and VRC16 antibodies bind WT gp120, but do not bind gp120 with a mutated CD4 binding site (FIGS. 16, 17, 22). ...
more infohttp://www.patentsencyclopedia.com/app/20150044137

The evolution of individual immunodeficiency virus type 1 (HIV-1) with respect - Pharmacodynamic Biomarker DevelopmentThe evolution of individual immunodeficiency virus type 1 (HIV-1) with respect - Pharmacodynamic Biomarker Development

Once gp120 binds towards the Compact disc4 molecule, the V1/V2 area, which offers been proven to communicate using the V3 loops ... The gp120-Compact disc4 discussion was also proven by experiments displaying a rise in particular antibody binding to ... unmasks the neighboring co-receptor binding sites consequently, therefore changing and rearranging the orientation from the ... between viral gp120 as well as the Compact disc4 molecule provides been shown to market the association from the gp120-Compact ...
more infohttp://www.woofahs.com/2017/06/19/the-evolution-of-individual-immunodeficiency-virus-type-1-hiv-1-with-respect/

Resource Providers
        
          at
          Montana State UniversityResource Providers at Montana State University

... dimensional shape of the CD4 binding site on gp120. This part of the molecule is conserved in structure, because all HIV use ... are also taking the synthetic peptide sequences and determining their three-dimensional structures when bound to the antibodies ... Comparing the structures of different antibodies to the CD4 binding site that vary significantly in their ability to neutralize ... Recently, we have initiated site-directed spin labeling (SDSL) of the ligand binding site in the formyl-peptide G-protein ...
more infohttp://montana.eagle-i.net/sweet/providers

HIV gp120 bound to CD4 antigenHIV gp120 bound to CD4 antigen

The binding site for the chemokine is induced after the CD4 antigen is bound. This site overlaps with the heavy chain of the ... You may want to turn the antibody chains off at this stage using these buttons: Heavy chain Light chain The molecule can be ... The gp120 is also shown bound to an induced neutralizing antibody (17b). At present a wire frame image of the structure of ... The CD4 antigen on the cell surface and the gp120 of the virus interact via a depression in the gp120 molecule that lacks ...
more infohttp://biomodel.uah.es/en/immuno/gp120-cd4-ab.htm
  • Impressively, antibody fragments such as bispecific T-cell engager, bispecific killer cell engager, trispecific killer cell engager, tandem diabody, and dual-affinity-retargeting are showing exciting results in terms of recruiting and activating self-immune effector cells to target and lyse tumor cells. (frontiersin.org)
  • The Fc region bears recognition motifs for binding innate immune receptors [Fcγ receptors (FcγRs), C1q, and neonatal Fc receptor (FcRn)] on an effector cell and thus is responsible for mediating immune effector functions and in vivo IgG stability ( 5 - 11 ). (frontiersin.org)
  • Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector cells (T cell, natural killer cell, or macrophage cell) toward target cells have shown great potential to maximize the benefits of antibody therapy. (frontiersin.org)
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